Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells.
Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells.
复制标题
间充质干细胞移植增加木瓜蛋白酶诱导的肺气肿肺中血管内皮生长因子的表达并抑制肺细胞凋亡。
DOI：
10.3109/14653241003745888
复制
发表时间：
2010-08
期刊：
影响因子：
4.5
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Xue Z;Zhang Z;Tang Z;Xu Y;Gu N;Zhen G;Zhao J
背景
肺气肿的特征是肺泡结构的丧失。我们发现骨髓间充质干细胞移植可改善木瓜蛋白酶诱导的肺气肿。然而，其潜在机制尚未完全了解。研究表明，阻断血管内皮生长因子（VEGF）信号通路导致肺细胞凋亡和肺气肿，MSC能够分泌VEGF。我们推测MSC移植可能通过增加VEGF-A表达和抑制肺细胞凋亡对肺气肿具有保护作用。
方法
我们检测了木瓜蛋白酶处理和MSC移植后大鼠肺组织的形态学和VEGF-A的表达。我们还使用了共培养系统，其中MSC和从木瓜蛋白酶处理的肺或对照肺制备的细胞一起培养。检测细胞和培养液中VEGF-A的含量，并检测培养肺细胞的凋亡情况。
结果
木瓜蛋白酶处理后大鼠肺组织VEGF-A表达降低，MSC移植可部分恢复VEGF-A表达。当MSC与从木瓜蛋白酶处理的肺制备的细胞共培养时，MSC的VEGF-A产生增加。此外，木瓜蛋白酶处理的肺细胞与MSC共培养时，细胞凋亡受到抑制。通过在培养基中加入抗肿瘤坏死因子（TNF）-α抗体，可抑制经木瓜蛋白酶处理的肺细胞诱导MSC产生VEGF-A。
结论
MSC移植对肺气肿的保护作用可能部分通过增加VEGF-A的表达和抑制肺细胞凋亡来实现。木瓜蛋白酶处理的肺细胞释放的TNF-α诱导MSC分泌VEGF-A。
BACKGROUND
Pulmonary emphysema is characterized by loss of alveolar structures. We have found that bone marrow (BM) mesenchymal stem cell (MSC) transplantation ameliorates papain-induced pulmonary emphysema. However, the underlying mechanism is not completely understood. It has been shown that blocking the vascular endothelial growth factor (VEGF) signaling pathway leads to apoptosis of lung cells and pulmonary emphysema, and MSC are capable of secreting VEGF. We hypothesized that MSC transplantation may have a protective effect on pulmonary emphysema by increasing VEGF-A expression and inhibiting apoptosis of lung cells.
METHODS
We examined the morphology and expression of VEGF-A in rat lung after papain treatment and MSC transplantation. We also used a co-culture system in which MSC and cells prepared from papain-treated lungs or control lungs were cultured together. The levels of VEGF-A in cells and culture medium were determined, and apoptosis of cultured lung cells was evaluated.
RESULTS
VEGF-A expression in rat lungs was decreased after papain treatment, which was partly rescued by MSC transplantation. MSC production of VEGF-A was increased when MSC were co-cultured with cells prepared from papain-treated lungs. Furthermore, the apoptosis of papain-treated lung cells was inhibited when co-cultured with MSC. The induction of MSC production of VEGF-A by papain-treated lung cells was inhibited by adding anti-tumor necrosis factor (TNF)-alpha antibody to the medium.
CONCLUSIONS
The protective effect of MSC transplantation on pulmonary emphysema may be partly mediated by increasing VEGF-A expression and inhibiting the apoptosis of lung cells. TNF-alpha released from papain-treated lung cells induces MSC to secret VEGF-A.
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影响因子：
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